The cellular events and molecular pathways leading to the detection, checkpoint response, and repair of spontaneous and double strand break induced DNA damage are not completely known. Although great strides have been made over the last few years, important repair pathways and genetic interactions are still being uncovered. A full understanding of all the genetic interactions in this area is an important goal, since DNA damage repair pathways are often genetically altered in cancer cells. Indeed, many of the genes involved in these pathways are themselves targets of chemotherapeutic drugs. The proposed work will reveal novel genetic relationships and pathways important for DNA replication, recombination, and repair, through a series of genetic and cell?biological experiments. The first set of experiments will explore the pathways involved in a phenotype known as Increased Recombination Centers (IRC), by performing a comprehensive epistasis analysis of IRC double mutants. The epistasis relationship amongst these genes will reveal which pathways they affect. The second line of inquiry will elucidate the relationship between the DNA damage response protein, Sml1, and the spindle assembly cell?cycle checkpoint (SAC). The proposed work will utilize a set of Sml1 separation of function mutants, and assess Sml1 chromatin localization and degradation patterns in the context of kinetochore and SAC mutants known to affect the degradation of Sml1. By studying this important DNA damage response gene, we will provide deeper insights in to the nature of cell cycle checkpoints. The combined experiments of this study will add significantly to our understanding of how DNA lesions are repaired.